rs10426628

Variant names:

• chr19-48589173-A-G
• rs10426628
• NM_177973.2:c.423+1736A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177973.2(SULT2B1):​c.423+1736A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,124 control chromosomes in the GnomAD database, including 47,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (47121 hom., cov: 31)
• Consequence: SULT2B1 NM_177973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 15 publications found

Genes affected

SULT2B1 (HGNC:11459): (sulfotransferase family 2B member 1) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

SULT2B1 Gene-Disease associations (from GenCC):

• ichthyosis, congenital, autosomal recessive 14

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	NM_177973.2	MANE Select	c.423+1736A>G		intron	N/A	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.378+1736A>G		intron	N/A	NP_004596.2	O00204-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.423+1736A>G		intron	N/A	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.378+1736A>G		intron	N/A	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+7573T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117699 AN: 152006 Hom.: 47067 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.774 AC: 117810 AN: 152124 Hom.: 47121 Cov.: 31 AF XY: 0.760 AC XY: 56560 AN XY: 74374

African (AFR) AF: 0.946 AC: 39312 AN: 41544

American (AMR) AF: 0.604 AC: 9230 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2569 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2470 AN: 5148

South Asian (SAS) AF: 0.606 AC: 2921 AN: 4824

European-Finnish (FIN) AF: 0.614 AC: 6503 AN: 10584

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52315 AN: 67962

Other (OTH) AF: 0.777 AC: 1639 AN: 2110

Alfa AF: 0.763 Hom.: 101539

Bravo AF: 0.780

Asia WGS AF: 0.591 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.51
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10426628; hg19: chr19-49092430;